Chem 232 D. J. Wardrop

wardropd@uic.edu

Problem Set 9

Question 1.

a. Rank in order of increasing number of chirality centers (1 = fewest chirality centers; 5 = most chirality).

Br

BrOHH3C

CH3

O

b. Rank in order of increasing rate of SN2 substitution (1 = slowest rate; 5 = fastest rate).

BrBr Br BrF

c. Rank the following molecular orbitals in order of decreasing energy (1 = highest energy; 4 = lowest energy)

d. Rank in order of increasing number of chirality centers (1 = fewest chirality centers; 5 = most chiralitycenters).

Cl Cl HO OHH H

Cl Cl

Cl

O

O

SO

e. Rank in order of increasing heat of hydrogenation (∆Hhydrog) (1 = lowest ∆Hhydrog, least exothermic; 5 = highest (∆Hhydrog, most exothermic).

f. Rank in order increasing stability (1 = least stable, highest energy; 4 = most stable, lowest energy).

CH3H

H

CH3

HH HCH3

H

H

CH3H

HH

CH3

HH

CH3

HH

CH3

HCH3

H

h. Rank in order of increasing index of hydrogen deficiency (IHD) (1 = lowest IHD; 5 = highest IHD).

HN

H3C O

O

CH3

Br BrCN

i. Considering only the most acidic proton in each molecule, rank in order of increasing acidity. (1 = least acidic, highest pKa; 5 = most acidic, lowest pKa).

H3C HH3C C

CH3H

HH3C OH

O

Cl3C OH

O

H3C OH

j. Rank in order of increasing rate of electrophilic aromatic substitution (SEAr) (1 = slowest rate; 5 = fastest rate).

H3C CH3

NH2

H

OH3C Cl Cl

Br

H3COH H3C CH3

CH3

Question 2

Draw the major organic product in the boxes provided for each reaction scheme below. If the reaction isregioselective, only draw the major product. Be sure to indicate the correct relative stereochemistry (i.e.dashes & wedges or axial & equatorial bonds) where appropriate.

OO

PhBr

NaN3

THF

For each of the transformations shown above, by what mechanism is product formed? (SN1, SN2, E1, or E2)

If the solvent was changed from THF to DMF would themechanism or rate of reaction change?

OO

PhOMs

NaCN

MeCN

OTsMe

OH

NaTHF

N

O

O

Br

HBr

25 °C

heat

CHCl3

HCl

-80 °C

OTf

KOt-Bu

THF

which hydrogensare more accesible?

Question 3

Draw the major Diels-Alder adducts in the boxes provided for each reaction scheme below. If thereaction is regioselective, only draw the major product. Be sure to indicate the correct relativestereochemistry (i.e. dashes & wedges or axial & equatorial bonds) where appropriate.

CO2Meheat

O

O

O

O

O

O

heat

heat

Which reaction will have the faster rate? Why?

heatCO2Me

O CO2Meheat

Question 4

Devise a synthesis for each of the target molecules (products) below. Write the forward synthesis fromthe reactant. Include all necessary conditions above/below the reaction arrow for each transformation.Write out the product for each transformation in your synthesis separately.

O Ph O Ph

H

CHO

O Ph

H

O PhMe

OH

O

Me

into

into

into

into

CO2Me

Ph

HH

MeO2C Ph

OHC CHO

CO2t-BuEt

HH

HHO

HMe

into

into

into

H

Cl

into

Why do you observe the relative stereochemistry in the product?

Question 5

a. Label each pair of molecules as one of the following: identical, conformational isomers, constitutional isomers, enantiomers, diastereomers, or geometrical isomers.

H CH3

H

CH3

ClH3C

H CH3

CH3

H Cl

CH3

OHHHH2N

CH3

HHONH2H

CH3

O NH2CH3

O

H3CNH2

HHO HO H

HHOOHH

O H

HHH

O

H

HO

OH

H

H

O

HH

O

b. Diels-Alder reactions are both regioselective and stereoselective. Use the Out-Endo-Cis rule to draw the endo regioisomeric product of the Diels-Alder reaction below. Hint: the electron withdrawing group on the dienophile is the endo group; the methyl groups on the diene are both out.

OCH3

OCH3

O

H

CH3

+heat

c. Determine whether hydroxide is a strong enough base to fully deprotonate the alkyne shown by calculating the Keq for the reaction. Show all work. Write the equation being used.

C CH H OH+Keq

C CH + H2O

pKa = 26 pKa = 15.7

c. Write the IUPAC name for the molecule below.

OH

d. Using the Frost Circle mnemonic, draw the molecular orbital diagram for a cyclopentadienyl carbanion (energy levels only). Indicate which MOs are bonding, non-bonding and anti-bonding.

Use up and down arrows to represent the electrons present in each orbital. State whether a cyclopentadienyl carbanion is aromatic, anti-aromatic or neither. Use your diagram to explain.

H

H H

HH

e. Write the IUPAC name for the molecule below.

OH

f. Draw a mechanism that accounts for the formation of 2-methyl-2-butanol from the hydrolysis (SN1) of 2-bromo-3-methylbutane.

g. An aqueous solution containing 10 g of optically pure (2S,3R)-2-chloro-5-hexyne-3-ol was diluted to 5 dL with CHCl3 and placed in a polarimeter tube 5 cm long. The measured rotation was –5.50º. Using the equation below, determine the specific rotation ([α]D). Hint: all values have been given withthe correct units for use in the equation below.

h. The solution above was mixed with 5 dL of a solution containing 20 g of racemic 2-chloro-5-hexyne-3-ol. Calculate the enantiomeric excess (ee) (optical purity) of this solution.

i. Draw the stereochemical structural formula for (2S,3R)-2-chloro-5-hexyne-3-ol.

l. How many total stereoisomers are possible for the structure below. Show your work for credit.

CH

CHCH2CH3

HC CH2

m. Streptimidone is an antibiotic and has the structure shown below. How many diastereomers of streptimidone are possible? How many enantiomers? Using the E-Z and R-S descriptors, specify all essential elements of stereochemistry of streptimidone.

NH

O

O

O

H3C

H

H HH3C

OHH

H

n. Draw Newman projections that sight down the C2-C3 bond for the three gauche conformations of 3-tert-butylhexane. Circle the most stable of those three conformations. Draw a square around the least stable of those three conformations.

o. Substitution of alkyl halides can compete with elimination as shown in the figure below. Clearly state three conditions (or circumstances) that favor substitution over elimination. Based on those conditions, draw the expected major product for the two reactions below.

Br

NaN3

Br

O CCH3

CH3

CH3K

1.

2.

3.

Question 6

Classify each of the reactions below as stereospecific (A), only stereoselective (B) or not stereoselective(C). Write the appropriate letter in the boxes next to each reaction. Only one letter should be written ineach box. Only the actual products isolated in each reaction is shown. In other words, if a product isn’tdrawn, it isn’t obtained by that reaction.

BrH3C

CH3

NaI, acetoneI CH3

H3C

CC CH3

Na, NH3 C C H

CH3

H

H3C

Cl H

HHCH3

CH3

H3C CH3

CH3H

H

NaOCH2CH3

CH3CH2OH

CH3Br

CH3CH2OH

ethanolysisCH3

OCH2CH3

CH3OCH2CH3

+

racemic mixture

Question 6 (contd)

Determine the relationship between each of the following six pairs of molecules. Classify them asconstitutional isomers (A), enantiomers (B), diastereomers (C), geometrical isomers (D), or not isomers(E). Write the letter corresponding to each classification in the boxes next to each pair. Only one lettershould be written in each box.

H CH3

H

CH3

ClH3C

H CH3

CH3

H Cl

CH3

OHHHH2N

CH3

HHONH2H

CH3

O NH2CH3

O

H3CNH2

HHO HO H

HHOOHH

O H

HHH

O

H

HO

OH

H

H

O

HH

O

In the right column, draw the stereoisomer indicated by the letter in each box. It may be helpful todetermine R or S for each chirality center to check your classification.

OH

O

OH

CH3H

B

D

BOH

O

OH

CH2OH

HO

HHOOHHOHHC

H OH

CH3 Cl

H

H3C

B

Question 7

Devise a synthesis for each of the target molecules (products) below. Write the forward synthesis fromthe reactant. Include all necessary conditions above/below the reaction arrow for each transformation.Write out the product for each transformation in your synthesis separately.

O

CO2MePh

O

HH

product

O

MeO2C

Ph

starting materials

O

H

H

O

OMeMe

N3

O

O

O

O

H

H

O

OMeMe

HO

intermediate

Question 8

A mixture containing both allylic bromides 1 and 2 undergoes solvolysis upon heating with isopropanolto provide a single product. The reaction is both regioselective and stereoselective. First, draw theproduct of solvolysis including the correct stereochemical notation. Then, draw a complete mechanism,beginning with 1, that includes curved arrow notation to show electron flow, shows all electron pairsbeing used in your mechanism and indicates charges where appropriate. Your mechanism shouldaccount for the fact that this reaction is both stereoselective and regioselective.

H3C

OH

CH3

heat+

1 2

Br Br

Methylcyclohexene (3) reacts with Br2 and H2O to form a vicinal halohydrin. The reaction is bothstereospecific and regioselective. First, draw the major product you would expect including correctregiochemistry and stereochemical notation (i.e. dashes and wedges). Then, draw a completemechanism that includes curved arrow notation to show electron flow, shows all electron pairs beingused in your mechanism and indicates charges where appropriate. Your mechanism should account forthe fact that this reaction is both stereospecific and regioselective. Hint: show the correctstereochemistry of the bromonium ion intermediate.

CH3 Br2 (no light)

H2O

3The following bromination reaction was carried out by as part of a study to prepare analogs of thecytotoxic microtubulin inhibitor, lavendustin A. In this case, substrate 4 undergoes benzylic brominationwhen heated with N-bromosuccinamide. In this case, NBS reacts to form bromine radicals (Br•) anddiatomic bromine (Br2) before bromination takes place. Draw a mechanism for the conversion of 4 to 5,which includes the formation of bromine and bromine radicals.

NO2CH3

OCH3

light (hv)

CCl4, reflux, 4 h53%

NO2CH2

OCH3

Br

CO2CH3 CO2CH3

steps

NH

OH

N

O

R

R'

Inhibitor of tubulinpolymerization4 5

N Br

O

O

tert-Butyl benzene (6) undergoes Friedel-Crafts acylation in the presence of AlCl3. Not surprisingly, thisreaction is highly regioselective and provides the para isomer as the major product. First, draw themajor product for this reaction. Second, draw the mechanism for the formation of the acylium ion whenpropanoyl chloride (7) reacts with AlCl3; show both resonance structures for the acylium ion. Finally,draw the mechanism for the reaction of toluene with the acylium ion to give the final product.

CH3H3CH3C

O

Cl+

AlCl3

6 7